Human studies utilizing functional magnetic resonance imaging (fMRI) have advanced our understanding of the regional and functional interplay between populations of neurons serving sensory, integrative and motor functions.
Changes in neuronal activity are accompanied by specific changes in hemodynamic functions such as cerebral blood flow, cerebral blood volume, and blood oxygenation. fMRI has been used to detect these physiologically induced changes in response to visual stimulation, somatosensory activation, motor tasks, and cognitive activity. During cognitive activity, the blood flow into the active region of the brain increases considerably compared with the tissue oxygen uptake which results in an increase in blood oxy-hemoglobin (HbO.sub.2) content. The susceptibility difference between diamagnetic oxy-hemoglobin and paramagnetic deoxy-hemoglobin (Hb) creates local magnetic field distortions that cause a dispersion in the processional frequency of the water protons and a concomitant change in the magnetic resonance (MR) signal intensity which is proportional to the ratio of HbO.sub.2 to Hb. These signal-intensity alterations related to blood oxygenation are termed the BOLD (blood oxygenation-level-dependent) effect. The voxels in which paramagnetic Hb content is decreased are illuminated in the image.
Unfortunately, extending these studies to animals has been difficult because technological limitations prevent restraining a conscious animal for prolonged periods of time in a magnetic resonance imaging (MRI) instrument. As a result most studies to date have been limited to animals which are typically anesthetized in order to minimize motion artifacts. In the last 5 years over 7,000 full length publications on MRI in animals have been written without a single reference to an awake animal. The low level of arousal during anesthesia either partially or completely suppresses the fMRI response and has impeded fMRl application to the more physiologically relevant functions that have been noted in humans.
Significant challenges remain in utilizing MRI techniques in both humans and anesthetized animals. One problem encountered in human studies has been artifacts from head movements. Studies in humans using invasive head fixation has shown improved image quality over non-invasive fixation and absence of fixation. However, this fixation method limits the amount of research time available for human subjects. On the other hand, animal studies must be performed under anesthetized conditions due to indiscriminate movement of conscious animals. Since image resolution is a salient feature of fMRI, precautions to ensure improved image quality with minimized head movements are essential. In addition to head movement, it has been observed that any motion outside the field of view can obscure or mimic the signal from neuronal activation.